Displaying publications 1 - 20 of 31 in total

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  1. Fulltext Effect of pyridostigmine (Mestinon) on human platelet aggregation
    Leong CF, Aini-Ardena M, Cheong SK, Norris N
    Malays J Pathol, 2009 Jun;31(1):45-52.
    PMID: 19694313 MyJurnal
    Normal platelet functions are critical for achieving primary haemostasis. Numerous medications have been shown to affect platelet functions. Pyridostigmine (Mestinon), an orally active cholinesterase inhibitor that is commonly used to treat myasthenia gravis has been documented to cause epistaxis and prolonged bleeding after a cut in anectodal reports. This study was initiated after a patient diagnosed to have myasthenia gravis, developed multiple bruises a week after being started on Mestinon. The objective of this study was to investigate the effect of Mestinon on platelet aggregation stimulated with various agonists in vitro.
    Matched MeSH terms: Blood Platelets/drug effects*
  2. Thrombocyte counts in mice after the administration of papaya leaf suspension
    Sathasivam K, Ramanathan S, Mansor SM, Haris MR, Wernsdorfer WH
    Wien Klin Wochenschr, 2009 Oct;121 Suppl 3:19-22.
    PMID: 19915811 DOI: 10.1007/s00508-009-1229-0
    Following up a popular use of crude leaf preparations from Carica papaya for the treatment of dengue infections, a suspension of powdered Carica papaya leaves in palm oil has been investigated for its effect on thrombocyte counts in mice, administering by gavage 15 mg of powdered leaves per kg body weight to 5 mice. Equal numbers of animals received corresponding volumes of either palm oil alone or physiological saline solution. Thrombocyte counts before and at 1, 2, 4, 8, 10, 12, 24, 48 and 72 hours after dosing revealed significantly higher mean counts at 1, 2, 4, 8, 10 and 12 after dosing with the C. papaya leaf formulation as compared to the mean count at hour 0. There was only a non-significant rise of thrombocyte counts in the group having received saline solution, possibly the expression of a normal circadian rhythm in mice. The group having received palm oil only showed a protracted increase of platelet counts that was significant at hours 8 and 48 and obviously the result of a hitherto unknown stimulation of thrombocyte release. The results call for a dose-response investigation and for extending the studies to the isolation and identification of the C. papaya substances responsible for the release and/or production of thrombocytes.
    Matched MeSH terms: Blood Platelets/drug effects*
  3. Fulltext Anti-inflammatory and antiplatelet activities of plasma are conserved across twelve mammalian species
    Ahmed S, Gul S, Idris F, Hussain A, Zia-Ul-Haq M, Jaafar HZ, et al.
    Molecules, 2014;19(8):11385-94.
    PMID: 25090125 DOI: 10.3390/molecules190811385
    Human plasma inhibits arachidonic acid metabolism and platelet aggregation. This helps human form a haemostatic control system that prevents the progress of certain aggregatory or inflammatory reactions. Whether this property of plasma is unique to human or extends to other species is not well known. It is speculated that this protective ability of plasma remains evolutionarily conserved in different mammals. In order to confirm this, the effect of plasma from 12 different mammalian species was investigated for its inhibitory potential against arachidonic acid metabolism and platelet aggregation. Metabolism of arachidonic acid by cyclooxygenase and lipoxygenase pathways was studies using radio-immuno assay and thin layer chromatography while platelet aggregation in the plasma of various mammals was monitored following turbedmetric method in a dual channel aggregometer. Results indicate that inhibition of AA metabolism and platelet aggregation is a common feature of plasma obtained from different mammalian species, although there exists large interspecies variation. This shows that besides human, other mammals also possess general protective mechanisms against various aggregatory and inflammatory conditions and this anti-inflammatory property of the plasma is evolutionarily conserved in mammalian species. The most likely candidates responsible for these properties of plasma include haptoglobin, albumin and lipoproteins.
    Matched MeSH terms: Blood Platelets/drug effects
  4. Fulltext Glycoprotein IIb/IIIa and P2Y12 induction by oligochitosan accelerates platelet aggregation
    Periayah MH, Halim AS, Yaacob NS, Saad AZ, Hussein AR, Rashid AH, et al.
    Biomed Res Int, 2014;2014:653149.
    PMID: 25247182 DOI: 10.1155/2014/653149
    Platelet membrane receptor glycoprotein IIb/IIIa (gpiibiiia) is a receptor detected on platelets. Adenosine diphosphate (ADP) activates gpiibiiia and P2Y12, causing platelet aggregation and thrombus stabilization during blood loss. Chitosan biomaterials were found to promote surface induced hemostasis and were capable of activating blood coagulation cascades by enhancing platelet aggregation. Our current findings show that the activation of the gpiibiiia complex and the major ADP receptor P2Y12 is required for platelet aggregation to reach hemostasis following the adherence of various concentrations of chitosan biomaterials [7% N,O-carboxymethylchitosan (NO-CMC) with 0.45 mL collagen, 8% NO-CMC, oligochitosan (O-C), and oligochitosan 53 (O-C 53)]. We studied gpiibiiia and P2Y12 through flow cytometric analysis and western blotting techniques. The highest expression of gpiibiiia was observed with Lyostypt (74.3 ± 7.82%), followed by O-C (65.5 ± 7.17%). Lyostypt and O-C resulted in gpiibiiia expression increases of 29.2% and 13.9%, respectively, compared with blood alone. Western blot analysis revealed that only O-C 53 upregulated the expression of P2Y12 (1.12 ± 0.03-fold) compared with blood alone. Our findings suggest that the regulation of gpiibiiia and P2Y12 levels could be clinically useful to activate platelets to reach hemostasis. Further, we show that the novel oligochitosan is able to induce the increased expression of gpiibiiia and P2Y12, thus accelerating platelet aggregation in vitro.
    Matched MeSH terms: Blood Platelets/drug effects
  5. Short-term estrogen replacement therapy reduces platelet marker levels in Malaysian postmenopausal women
    Sheikh SA, Roshan TM, Khattak MN, Baig AA, Noor SJ, Hassan R, et al.
    Menopause Int, 2011 Mar;17(1):6-10.
    PMID: 21427417 DOI: 10.1258/mi.2011.011001
    In healthy postmenopausal women (PMW) increased platelet activation has been associated with adverse cardiovascular events. There is much debate about the relationship between platelet function and serum estradiol level in PMW. This study assessed the effect of short-term oral estrogen replacement therapy (ERT) on platelet activation markers (CD62P and PAC-1) and its correlation with age and body mass index (BMI) among healthy PMW.
    Matched MeSH terms: Blood Platelets/drug effects*
  6. Coagulation studies in Asian women using injectable progestogen for contraception
    Tsakok FH, Koh S, Yuen R, Ratnam SS
    Int J Gynaecol Obstet, 1980 9 1;18(2):105-8.
    PMID: 6108245 DOI: 10.1002/j.1879-3479.1980.tb00256.x
    Coagulation, fibrinolytic activity and platelet function were studied in 104 Asian women volunteers who received 150 mg of depot medroxyprogesterone acetate intramuscularly every three months for two years or more. The results were compared with those in matched controls. There was a paucity of change in coagulation factors. The fibrinogen levels were increased and prothrombin time was shortened. The fibrinolytic activity, as shown by the euglobulin clot lysis time, was significantly increased. This latter change contrasts with the many reports concerning Caucasian women and may reflect an increase in fibrinolytic potential in Asian women.
    Matched MeSH terms: Blood Platelets/drug effects
  7. Fulltext Effect of ultrapure lipopolysaccharides derived from diverse bacterial species on the modulation of platelet activation
    Vallance TM, Ravishankar D, Albadawi DAI, Layfield H, Sheard J, Vaiyapuri R, et al.
    Sci Rep, 2019 12 03;9(1):18258.
    PMID: 31796818 DOI: 10.1038/s41598-019-54617-w
    Platelets are small circulating blood cells that play essential roles in the maintenance of haemostasis via blood clotting. However, they also play critical roles in the regulation of innate immune responses. Inflammatory receptors, specifically Toll-like receptor (TLR)-4, have been reported to modify platelet reactivity. A plethora of studies have reported controversial functions of TLR4 in the modulation of platelet function using various chemotypes and preparations of its ligand, lipopolysaccharide (LPS). The method of preparation of LPS may explain these discrepancies however this is not fully understood. Hence, to determine the impact of LPS on platelet activation, we used ultrapure preparations of LPS from Escherichia coli (LPSEC), Salmonella minnesota (LPSSM), and Rhodobacter sphaeroides (LPSRS) and examined their actions under diverse experimental conditions in human platelets. LPSEC did not affect platelet activation markers such as inside-out signalling to integrin αIIbβ3 or P-selectin exposure upon agonist-induced activation in platelet-rich plasma or whole blood whereas LPSSM and LPSRS inhibited platelet activation under specific conditions at supraphysiological concentrations. Overall, our data demonstrate that platelet activation is not largely influenced by any of the ultrapure LPS chemotypes used in this study on their own except under certain conditions.
    Matched MeSH terms: Blood Platelets/drug effects
  8. Late stent thrombosis in a patient with CYP2C19*3/*17 genotype and clopidogrel high on-treatment platelet reactivity
    Tan SSN, Koh KT, Tiong LL, Ong TK, Fong AYY
    Pharmacogenomics, 2018 10;19(15):1151-1157.
    PMID: 30191759 DOI: 10.2217/pgs-2018-0082
    AIM: Recurrent thrombotic events still occur despite dual antiplatelet therapy in patient's post percutaneous coronary intervention (PCI) could be attributed to high on-treatment platelet reactivity.

    METHODS: A 44-year-old male, who had staged PCI to left anterior descending (LAD) 2 weeks after an anterior MI, with a drug-coated stent was readmitted with new anterior STEMI 35 days later. Coronary angiogram revealed mid-stent thrombus in situ. He had further uncomplicated PCI. Platelet function testing and genotyping showed clopidogrel high on-treatment platelet reactivity and CYP2C19*3/*17 genotype. Ticagrelor was commenced.

    RESULTS & CONCLUSION: This case study is the first reported in Malaysia to document a patient with a CYP2C19*3/*17 genotype presenting with a stent thrombosis after an uncomplicated index PCI procedure.

    Matched MeSH terms: Blood Platelets/drug effects*
  9. Physicochemical evaluation and in vitro hemocompatibility study on nanoporous hydroxyapatite
    Ooi CH, Ling YP, Abdullah WZ, Mustafa AZ, Pung SY, Yeoh FY
    J Mater Sci Mater Med, 2019 Mar 30;30(4):44.
    PMID: 30929088 DOI: 10.1007/s10856-019-6247-5
    Hydroxyapatite is an ideal biomaterial for bone tissue engineering due to its biocompatibility and hemocompatibility which have been widely studied by many researchers. The incorporation of nanoporosity into hydroxyapatite could transform the biomaterial into an effective adsorbent for uremic toxins removal especially in artificial kidney system. However, the effect of nanoporosity incorporation on the hemocompatibility of hydroxyapatite has yet to be answered. In this study, nanoporous hydroxyapatite was synthesized using hydrothermal technique and its hemocompatibility was determined. Non-ionic surfactants were used as soft templates to create porosity in the hydroxyapatite. The presence of pure hydroxyapatite phase in the synthesized samples is validated by X-ray diffraction analysis and Fourier transform infrared spectroscopy. The TEM images show that the hydroxyapatite formed rod-like particles with the length of 21-90 nm and diameter of 11-70 nm. The hydroxyapatite samples exhibit BET surface area of 33-45 m2 g-1 and pore volume of 0.35-0.44 cm3 g-1. The hemocompatibility of the hydroxyapatite was determined via hemolysis test, platelet adhesion, platelet activation and blood clotting time measurement. The nanoporous hydroxyapatite shows less than 5% hemolysis, suggesting that the sample is highly hemocompatible. There is no activation and morphological change observed on the platelets adhered onto the hydroxyapatite. The blood clotting time demonstrates that the blood incubated with the hydroxyapatite did not coagulate. This study summarizes that the synthesized nanoporous hydroxyapatite is a highly hemocompatible biomaterial and could potentially be utilized in biomedical applications.
    Matched MeSH terms: Blood Platelets/drug effects*
  10. The effect of CYP2C19 genetic polymorphism and non-genetic factors on clopidogrel platelets inhibition in East Asian coronary artery disease patients
    Amin AM, Sheau Chin L, Mohamed Noor DA, Mostafa H, Abdul Kader MASK, Kah Hay Y, et al.
    Thromb Res, 2017 10;158:22-24.
    PMID: 28802144 DOI: 10.1016/j.thromres.2017.07.032
    Matched MeSH terms: Blood Platelets/drug effects*
  11. Fulltext Impact of specific functional groups in flavonoids on the modulation of platelet activation
    Ravishankar D, Salamah M, Akimbaev A, Williams HF, Albadawi DAI, Vaiyapuri R, et al.
    Sci Rep, 2018 Jun 22;8(1):9528.
    PMID: 29934595 DOI: 10.1038/s41598-018-27809-z
    Flavonoids exert innumerable beneficial effects on cardiovascular health including the reduction of platelet activation, and thereby, thrombosis. Hence, flavonoids are deemed to be a molecular template for the design of novel therapeutic agents for various diseases including thrombotic conditions. However, the structure-activity relationships of flavonoids with platelets is not fully understood. Therefore, this study aims to advance the current knowledge on structure-activity relationships of flavonoids through a systematic analysis of structurally-related flavones. Here, we investigated a panel of 16 synthetic flavones containing hydroxy or methoxy groups at C-7,8 positions on the A-ring, with a phenyl group or its bioisosteres as the B-ring, along with their thio analogues possessing a sulfur molecule at the 4th carbon position of the C-ring. The antiplatelet efficacies of these compounds were analysed using human isolated platelets upon activation with cross-linked collagen-related peptide by optical aggregometry. The results demonstrate that the hydroxyl groups in flavonoids are important for optimum platelet inhibitory activities. In addition, the 4-C=O and B ring phenyl groups are less critical for the antiplatelet activity of these flavonoids. This structure-activity relationship of flavonoids with the modulation of platelet function may guide the design, optimisation and development of flavonoid scaffolds as antiplatelet agents.
    Matched MeSH terms: Blood Platelets/drug effects
  12. Inhibitory effects of compounds from Zingiberaceae species on platelet activating factor receptor binding
    Jantan I, Pisar M, Sirat HM, Basar N, Jamil S, Ali RM, et al.
    Phytother Res, 2004 Dec;18(12):1005-7.
    PMID: 15742349
    Ten compounds isolated from Alpinia mutica Roxb., Curcuma xanthorrhiza Roxb. and Kaempferia rotunda Linn. (Family: Zingiberaceae) were investigated for their platelet-activating factor (PAF) antagonistic activities on rabbit platelets using 3H-PAF as a ligand. Among them, four compounds showed significant inhibitory effects. Alpinetin and 5,6-dehydrokawain isolated from A. mutica exhibited IC50 values of 41.6 and 59.3 microM, respectively. The IC50 values of 3-deacetylcrotepoxide and 2-hydroxy-4,4',6'-trimethoxychalcone from K. rotunda were 45.6 and 57.4 microM, respectively. 1-Methoxy-2-methyl-5-(1',5'-dimethylhex-4'-enyl)-benzene, synthesized by methylation of xanthorrhizol which was obtained from C. xanthorrhiza, showed an IC50 value of 40.9 microM. The results indicated that these compounds were relatively strong PAF receptor binding inhibitors.
    Matched MeSH terms: Blood Platelets/drug effects*
  13. Fulltext Effects of chalcone derivatives on players of the immune system
    Lee JS, Bukhari SN, Fauzi NM
    Drug Des Devel Ther, 2015;9:4761-78.
    PMID: 26316713 DOI: 10.2147/DDDT.S86242
    The immune system is the defense mechanism in living organisms that protects against the invasion of foreign materials, microorganisms, and pathogens. It involves multiple organs and tissues in human body, such as lymph nodes, spleen, and mucosa-associated lymphoid tissues. However, the execution of immune activities depends on a number of specific cell types, such as B cells, T cells, macrophages, and granulocytes, which provide various immune responses against pathogens. In addition to normal physiological functions, abnormal proliferation, migration, and differentiation of these cells (in response to various chemical stimuli produced by invading pathogens) have been associated with several pathological disorders. The unwanted conditions related to these cells have made them prominent targets in the development of new therapeutic interventions against various pathological implications, such as atherosclerosis and autoimmune diseases. Chalcone derivatives exhibit a broad spectrum of pharmacological activities, such as immunomodulation, as well as anti-inflammatory, anticancer, antiviral, and antimicrobial properties. Many studies have been conducted to determine their inhibitory or stimulatory activities in immune cells, and the findings are of significance to provide a new direction for subsequent research. This review highlights the effects of chalcone derivatives in different types of immune cells.
    Matched MeSH terms: Blood Platelets/drug effects
  14. Effect of the Novel Biodegradable N, O-Carboxymethylchitosan and Oligo-Chitosan on the Platelet Thrombogenicity Cascade in von Willebrand Disease
    Periayah MH, Halim AS, Mat Saad AZ, Yaacob NS, Hussein AR, Abdul Karim F, et al.
    Thromb Res, 2015 Sep;136(3):625-33.
    PMID: 26254703 DOI: 10.1016/j.thromres.2015.07.027
    Von Willebrand disease (vWD) is the second least common hemostatic disorder in Malaysia, and it has a low prevalence. This study examined the underlying platelet thrombogenicity cascades in the presence of different formulations of chitosan-derivatives in vWD patients. This paper aimed to determine the significant influence of chitosan biomaterial in stimulating the platelet thrombogenicity cascades that involve the von Willebrand factor, Factor 8, Thromboxane A2, P2Y12 and Glycoprotein IIb/IIIa in vWD.
    Matched MeSH terms: Blood Platelets/drug effects*
  15. Fulltext Ruthenium-conjugated chrysin analogues modulate platelet activity, thrombus formation and haemostasis with enhanced efficacy
    Ravishankar D, Salamah M, Attina A, Pothi R, Vallance TM, Javed M, et al.
    Sci Rep, 2017 07 18;7(1):5738.
    PMID: 28720875 DOI: 10.1038/s41598-017-05936-3
    The constant increase in cardiovascular disease rate coupled with significant drawbacks of existing therapies emphasise the necessity to improve therapeutic strategies. Natural flavonoids exert innumerable pharmacological effects in humans. Here, we demonstrate the effects of chrysin, a natural flavonoid found largely in honey and passionflower on the modulation of platelet function, haemostasis and thrombosis. Chrysin displayed significant inhibitory effects on isolated platelets, however, its activity was substantially reduced under physiological conditions. In order to increase the efficacy of chrysin, a sulfur derivative (thio-chrysin), and ruthenium-complexes (Ru-chrysin and Ru-thio-chrysin) were synthesised and their effects on the modulation of platelet function were evaluated. Indeed, Ru-thio-chrysin displayed a 4-fold greater inhibition of platelet function and thrombus formation in vitro than chrysin under physiologically relevant conditions such as in platelet-rich plasma and whole blood. Notably, Ru-thio-chrysin exhibited similar efficacy to chrysin in the modulation of haemostasis in mice. Increased bioavailability and cell permeability of Ru-thio-chrysin compared to chrysin were found to be the basis for its enhanced activity. Together, these results demonstrate that Ru-thio-coupled natural compounds such as chrysin may serve as promising templates for the development of novel anti-thrombotic agents.
    Matched MeSH terms: Blood Platelets/drug effects*
  16. Fulltext Prevailing Knowledge on the Bioavailability and Biological Activities of Sulphur Compounds from Alliums: A Potential Drug Candidate
    Subramanian MS, Nandagopal Ms G, Amin Nordin S, Thilakavathy K, Joseph N
    Molecules, 2020 Sep 09;25(18).
    PMID: 32916777 DOI: 10.3390/molecules25184111
    Allium sativum (garlic) is widely known and is consumed as a natural prophylactic worldwide. It produces more than 200 identified chemical compounds, with more than 20 different kinds of sulfide compounds. The sulfide compounds particularly are proven to contribute to its various biological roles and pharmacological properties such as antimicrobial, antithrombotic, hypoglycemic, antitumour, and hypolipidemic. Therefore, it is often referred as disease-preventive food. Sulphur-containing compounds from A. sativum are derivatives of S-alkenyl-l-cysteine sulfoxides, ajoene molecules, thiosulfinates, sulfides, and S-allylcysteine. This review presents an overview of the water-soluble and oil-soluble sulphur based phytochemical compounds present in garlic, highlighting their mechanism of action in treating various health conditions. However, its role as a therapeutic agent should be extensively studied as it depends on factors such as the effective dosage and the suitable method of preparation.
    Matched MeSH terms: Blood Platelets/drug effects
  17. Platelet-activating factor (PAF) receptor binding antagonist activity of the methanol extracts and isolated flavonoids from Chromolaena odorata (L.) King and Robinson
    Ling SK, Pisar MM, Man S
    Biol Pharm Bull, 2007 Jun;30(6):1150-2.
    PMID: 17541171
    The leaf, stem and root extracts of Chromolaena odorata were evaluated for their effect on platelet-activating factor (PAF) receptor binding on rabbit platelets using 3H-PAF as a ligand. The leaf extract demonstrated high PAF receptor binding inhibitory activity of 79.2+/-2.1% at 18.2 microg/ml. A total of eleven flavonoids were subsequently isolated from the active leaf extract and evaluated for their effects on PAF receptor binding. Eight of the flavonoids exhibited >50% inhibition on the binding activity at 18.2 microg/ml. These flavonoids were identified as eriodictyol 7,4'-dimethyl ether, quercetin 7,4'-methyl ether, naringenin 4'-methyl ether, kaempferol 4'-methyl ether, kaempferol 3-O-rutinoside, taxifolin 4'-methyl ether, taxifolin 7-methyl ether and quercetin 4'-methyl ether. Their IC50 values ranged from 19.5 to 62.1 microM.
    Matched MeSH terms: Blood Platelets/drug effects
  18. Fulltext Effect of Carica papaya Leaf Extract Capsule on Platelet Count in Patients of Dengue Fever with Thrombocytopenia
    Gadhwal AK, Ankit BS, Chahar C, Tantia P, Sirohi P, Agrawal RP
    J Assoc Physicians India, 2016 06;64(6):22-26.
    PMID: 27739263
    OBJECTIVE: Thrombocytopenia in dengue fever is a common and serious complication. However, no specific treatment is available for dengue fever induced thrombocytopenia. In few countries (Pakistan, Malaysia, Sri Lanka and other Asian countries) the leaf extract of Carica papaya has been effectively used for thrombocytopenia. So, the study is planned to access effect of Carica papaya leaf extract on platelet count in dengue fever patients.

    METHODS: All participants were randomised into two groups, study group and control group; the study group was given papaya leaf extract capsule of 500 mg once daily and routine supportive treatment for consecutive five days. The controls were given only routine supportive treatment. Daily complete blood counts, platelet counts and haematocrit level, liver function test, renal function test of both groups were observed.

    RESULTS: On the first day platelet count of study group and control group was (59.82±18.63, 61.06±20.03 thousands, p value 0.36). On the 2nd day platelet count of both study and control groups was not significantly different (61.67±19.46 and 59.93±19.52 thousands, p value 0.20) but on 3rd day platelet count of study group was significantly higher than control group (82.96±16.72, 66.45±17.36 thousands, p value < 0.01). On 4th and 5th day platelet count of study group (122.43±19.36 and 112.47±17.49 thousands respectively) was also significantly higher than the control group (88.75±21.65 and 102.59±19.35 thousands) (p value < 0.01). On 7th day platelet count of study group and control group were not significantly different (124.47±12.35 and 122.46±19.76 thousands respectively, p value 0.08). Average hospitalization period of study group v/s control group was 3.65±0.97 v/s 5.42±0.98 days (p value < 0.01). Average platelet transfusion requirement in study group was significantly less than control group (0.685 units per patient v/s 1.19 units per patient) (p value <0.01).

    CONCLUSIONS: It is concluded that Carica papaya leaf extract increases the platelet count in dengue fever without any side effect and prevents the complication of thrombocytopenia. So, it can be used in dengue fever with thrombocytopenia patients.
    Matched MeSH terms: Blood Platelets/drug effects*
  19. 1H NMR based pharmacometabolomics analysis of urine identifies metabolic phenotype of clopidogrel high on treatment platelets reactivity in coronary artery disease patients
    Amin AM, Sheau Chin L, Teh CH, Mostafa H, Mohamed Noor DA, Sk Abdul Kader MA, et al.
    J Pharm Biomed Anal, 2017 Nov 30;146:135-146.
    PMID: 28873361 DOI: 10.1016/j.jpba.2017.08.018
    Clopidogrel high on treatment platelets reactivity (HTPR) has burdened achieving optimum therapeutic outcome. Although there are known genetic and non-genetic factors associated with clopidogrel HTPR, which explain in part clopidogrel HTPR, yet, great portion remains unknown, often hindering personalizing antiplatelet therapy. Nuclear magnetic resonance (1H NMR) pharmacometabolomics analysis is useful technique to phenotype drug response. We investigated using 1H NMR analysis to phenotype clopidogrel HTPR in urine. Urine samples were collected from 71 coronary artery disease (CAD) patients who were planned for interventional angiographic procedure prior to taking 600mg clopidogrel loading dose (LD) and 6h post LD. Patients' platelets function testing was assessed with the VerifyNow® P2Y12 assay at 6h after LD. Urine samples were analysed using 1H NMR. Multivariate statistical analysis was used to identify metabolites associated with clopidogrel HTPR. In pre-dose samples, 16 metabolites were associated with clopidogrel HTPR. However, 18 metabolites were associated with clopidogrel HTPR in post-dose samples. The pathway analysis of the identified biomarkers reflected that multifactorial conditions are associated with clopidogrel HTPR. It also revealed the implicated role of gut microbiota in clopidogrel HTPR. Pharmacometabolomics not only discovered novel biomarkers of clopidogrel HTPR but also revealed implicated pathways and conditions.
    Matched MeSH terms: Blood Platelets/drug effects*
  20. Antithrombocytopenic activity of carpaine and alkaloidal extract of Carica papaya Linn. leaves in busulfan induced thrombocytopenic Wistar rats
    Zunjar V, Dash RP, Jivrajani M, Trivedi B, Nivsarkar M
    J Ethnopharmacol, 2016 Apr 02;181:20-5.
    PMID: 26812680 DOI: 10.1016/j.jep.2016.01.035
    ETHNOPHARMACOLOGICAL RELAVANCE: The decoction of Carica papaya Linn. leaves is used in folklore medicine in certain parts of Malaysia and Indonesia for the treatment of different types of thrombocytopenia associated with diseases and drugs. There are several scientific studies carried out on humans and animal models to confirm the efficacy of decoction of papaya leave for the treatment of disease induced and drug induced thrombocytopenia, however very little is known about the bio-active compounds responsible for the observed activity. The aim of present study was to identify the active phytochemical component of Carica papaya Linn. leaves decoction responsible for anti-thrombocytopenic activity in busulfan-induced thrombocytopenic rats.

    MATERIALS AND METHODS: Antithrombocytopenic activity was assessed on busulfan induced thrombocytopenic Wistar rats. The antithrombocytopenic activity of different bio-guided fractions was evaluated by monitoring blood platelet count. Bioactive compound carpaine was isolated and purified by chromatographic methods and confirmed by spectroscopic methods (LC-MS and 1D/2D-1H/13C NMR) and the structure was confirmed by single crystal X-ray diffraction. Quantification of carpaine was carried out by LC-MS/MS equipped with XTerra(®) MS C18 column and ESI-MS detector using 90:10 CH3CN:CH3COONH4 (6mM) under isocratic conditions and detected with multiple reaction monitoring (MRM) in positive ion mode.

    RESULTS: Two different phytochemical groups were isolated from decoction of Carica papaya leaves: phenolics, and alkaloids. Out of these, only alkaloid fraction showed good biological activity. Carpaine was isolated from the alkaloid fraction and exhibited potent activity in sustaining platelet counts upto 555.50±85.17×10(9)/L with no acute toxicity.

    CONCLUSIONS: This study scientifically validates the popular usage of decoction of Carica papaya leaves and it also proves that alkaloids particularly carpaine present in the leaves to be responsible for the antithrombocytopenic activity.

    Matched MeSH terms: Blood Platelets/drug effects
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